What is bronchiolitis?
Bronchiolitis is a common illness affecting the lower (smaller) respiratory airways in infants (younger than 24 months of age). Usually caused by a viral infection, it results in breathing problems, including coughing, fast breathing, and wheezing, and can cause poor feeding. It is a major cause of hospitalisation in infants. The treatment of bronchiolitis is supportive. For those who require hospitalisation, this involves helping infants to breathe until the infection clears. An increasingly used method to support breathing is blended, heated, humidified air and oxygen, through nasal cannulae (tubes) at flow rates higher than two litres of air/oxygen per minute, which is the maximum for conventional (low-flow) dry oxygen delivery. This is known as high-flow nasal cannula therapy, and it allows the comfortable delivery of high flow rates of an air/oxygen blend, which may improve ventilation. Continuous positive airway pressure (CPAP) is also increasingly used in the treatment of bronchiolitis. It involves delivering a blend of air/oxygen at a preset pressure to hold the airways open and prevent collapse during expiration (breathing out).
What did we want to find out?
High-flow oxygen therapy may lead to a reduced need for invasive respiratory support (e.g. intubation) and may have a clinical advantage over other treatments by preventing drying of the upper airway. This review assessed the effects of high-flow nasal cannula therapy, compared with other respiratory support, in the treatment of infants with bronchiolitis.
What did we do?
Sixteen studies (2813 participants) met our inclusion criteria. These studies compared either high-flow to conventional oxygen therapy (low-flow) or continuous positive airway pressure (CPAP). These studies were based in paediatric wards and intensive care units around the world. We identified 11 trials comparing high-flow to low-flow, involving a total of 2322 infants, and five studies involving a total of 491 infants comparing high-flow to CPAP. In each study we focussed on comparing length of hospital stay, changes in heart rate, respiratory rate, and clinical scoring criteria, as well as numbers of adverse events and need for treatment to be escalated. We analysed these data to determine whether either intervention was superior and any differences were statistically significant.
What did we find?
We divided our review into studies comparing high-flow to low-flow, and studies comparing high-flow to CPAP.
When comparing high-flow to low-flow, we found a difference, favouring high-flow, with a reduction in the length of hospital stay and the duration of oxygen therapy.
The reduction in the length of hospital stay was found to be 0.65 days (15.6 hours), and the reduction in the duration of oxygen therapy was 0.59 days (14.2 hours). These reductions are modest and may not have significant clinical impact when applied in the real world.
We also found a difference, favouring high-flow, in a greater reduction in respiratory and heart rates, as well as fewer incidences of need to escalate treatment.
We did not find a difference between the high-flow and low-flow groups in the incidence of adverse events (including medical events such as bleeding and lung collapse, as well as equipment issues).
In all studies, high-flow was generally well tolerated with no serious adverse events recorded when compared to low-flow and CPAP.
We did not have enough studies comparing high-flow to CPAP to be able to compare or combine results (meta-analysis).
What are the limitations of the evidence?
High-flow nasal cannula oxygen is more effective than low-flow in terms of reduction in respiratory and heart rates, length of hospital stay, and duration of oxygen therapy, as well as the need for treatment escalation. Due to considerable differences between studies (heterogeneity), as well as risk of biases, we are only moderately confident in the evidence found for many of these outcomes.
There is insufficient evidence to determine the effectiveness of high-flow nasal cannula therapy when compared to CPAP for the treatment of bronchiolitis in infants and further studies are required to determine its role.
How up-to-date is this evidence?
This evidence is current to 8 December 2022.
High-flow nasal cannula therapy may have some benefits over low-flow oxygen for infants with bronchiolitis in terms of a greater improvement in respiratory and heart rates, as well as a modest reduction in the length of hospital stay and duration of oxygen therapy, with a reduced incidence of treatment escalation. There does not appear to be a difference in the number of adverse events.
Further studies comparing high-flow nasal cannula therapy and CPAP are required to demonstrate the efficacy of one modality over the other. A standardised clinical definition of bronchiolitis, as well as the use of a validated clinical severity score, would allow for greater and more accurate comparison between studies.
Bronchiolitis is a common lower respiratory tract illness, usually of viral aetiology, affecting infants younger than 24 months of age and is the most common cause of hospitalisation of infants. It causes airway inflammation, mucus production and mucous plugging, resulting in airway obstruction. Effective pharmacotherapy is lacking and bronchiolitis is a major cause of morbidity and mortality.
Conventional treatment consists of supportive therapy in the form of fluids, supplemental oxygen, and respiratory support. Traditionally, oxygen delivery is as a dry gas at 100% concentration via low-flow nasal prongs. However, the use of heated, humidified, high-flow nasal cannula (HFNC) therapy enables delivery of higher inspired gas flows of an air/oxygen blend, at 2 to 3 L/kg per minute up to 60 L/min in children. It can provide some level of continuous positive airway pressure (CPAP) to improve ventilation in a minimally invasive manner. This may reduce the need for invasive respiratory support, thus potentially lowering costs, with clinical advantages and fewer adverse effects.
To assess the effects of HFNC therapy compared with conventional respiratory support in the treatment of infants with bronchiolitis.
We searched CENTRAL, MEDLINE, Embase, CINAHL, LILACS, and Web of Science (from June 2013 to December 2022). In addition, we consulted ongoing trial registers and experts in the field to identify ongoing studies, checked reference lists of relevant articles, and searched for conference abstracts. Date restrictions were imposed such that we only searched for studies published after the original version of this review.
We included randomised controlled trials (RCTs) or quasi-RCTs that assessed the effects of HFNC (delivering oxygen or oxygen/room air blend at flow rates greater than 4 L/minute) compared to conventional treatment in infants (< 24 months) with a clinical diagnosis of bronchiolitis.
Two review authors independently used a standard template to assess trials for inclusion and extract data on study characteristics, risk of bias elements, and outcomes. We contacted trial authors to request missing data. Outcome measures included the need for invasive respiratory support and time until discharge, clinical severity measures, oxygen saturation, duration of oxygen therapy, and adverse events.
In this update we included 15 new RCTs (2794 participants), bringing the total number of RCTs to 16 (2813 participants). Of the 16 studies, 11 compared high-flow to low-flow, and five compared high-flow to CPAP. These studies included infants less than 24 months of age as stated in our selection criteria. There were no significant differences in sex.
We found that when comparing high-flow to low-flow oxygen therapy for infants with bronchiolitis there may be a reduction in the total length of hospital stay (mean difference (MD) -0.65 days, 95% confidence interval (CI) -1.23 to -0.06; P < 0.00001, I2 = 89%; 7 studies, 1951 participants; low-certainty evidence). There may also be a reduction in the duration of oxygen therapy (MD -0.59 days, 95% CI -1 to -0.18; P < 0.00001, I2 = 86%; 7 studies, 2132 participants; low-certainty evidence).
We also found that there was probably an improvement in respiratory rate at one and 24 hours, and heart rate at one, four to six, and 24 hours in those receiving high-flow oxygen therapy when compared to pre-intervention baselines. There was also probably a reduced risk of treatment escalation in those receiving high-flow when compared to low-flow oxygen therapy (risk ratio (RR) 0.55, 95% CI 0.39 to 0.79; P = 0.001, I2 = 43%; 8 studies, 2215 participants; moderate-certainty evidence).
We found no difference in the incidence of adverse events (RR 1.2, 95% CI 0.38 to 3.74; P = 0.76, I2 = 26%; 4 studies, 1789 participants; low-certainty evidence) between the two groups.
The lack of comparable outcomes in studies comparing high-flow and CPAP, as well as the small numbers of participants, limited our ability to perform meta-analysis on this group.